This project is concerned with 1) the systematic definition and characterization of the small-granule, presumptively endocrine cells of the mammalian lung; 2) the fetal development and maturation of these cells and their subsequent turnover in the adult; 3) the origin of endocrine-cell human lung tumors and improved methods for their diagnosis. Recently, we have developed two simple, reliable light microscopic methods for demonstrating small-granule cells in glycol methacrylate-embedded lungs of hamsters, rabbits, mice and cats and in a variety of human pulmonary tumors: 1) PAS-lead hematoxylin staining, and 2) a stable, aqueous formaldehyde-induced serotonin fluorescence. With these methods, we will continue systematic studies of the distribution of small-granule cells in hamster and mouse lungs using 3-dimensional airway reconstructions. Written descriptions for data analysis include the number and staining characteristics of endocrine cells; their position in the airway with respect to branch points, bronchiolar-alveolar portals; airway branching order and size; the nature of immediately adjacent epithelial cells; the presence or absence of underlying smooth muscle, nerves and vessels. Coordinated electron microscopy also will be carried out as will trial immunocytochemical localizations for hormones produced ectopically by lung tumors. Serotonin fluorescence, argyrophil and PAS-lead hematoxylin methods will be applied conjunctively to study fetal development and maturation of these cells in fetal hamster lung and will be coupled with autoradiographic studies of cell turnover in the adult. Conjunctive light microscopic staining and electron microscopy will be applied to human lung tumors to characterize their constituent cells and to investigate their relationship with normal elements of the bronchial epithelium.